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                <title level="j">Histopathology</title>
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                <term xml:lang="en">head and neck</term>
                <term xml:lang="en">grading</term>
                <term xml:lang="en">dysplasia</term>
                <term xml:lang="en">diagnosis</term>
                <term xml:lang="en">deep learning</term>
                <term xml:lang="en">computational pathology</term>
                <term xml:lang="en">AI confidence</term>
                <term xml:lang="en">AI assistance</term>
                <term xml:lang="en">AI assistance AI confidence computational pathology deep learning diagnosis dysplasia grading head and neck</term>
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              <p>Background Diagnosis of head and neck (HN) squamous dysplasias and carcinomas is critical for patient care, cure, and follow‐up. It can be challenging, especially for grading intraepithelial lesions. Despite recent simplification in the last WHO grading system, the inter‐ and intraobserver variability remains substantial, particularly for nonspecialized pathologists, exhibiting the need for new tools to support pathologists. Methods In this study we investigated the potential of deep learning to assist the pathologist with automatic and reliable classification of HN lesions following the 2022 WHO classification system. We created, for the first time, a large‐scale database of histological samples (&gt;2000 slides) intended for developing an automatic diagnostic tool. We developed and trained a weakly supervised model performing classification from whole‐slide images (WSI). We evaluated our model on both internal and external test sets and we defined and validated a new confidence score to assess the predictions that can be used to identify difficult cases. Results Our model demonstrated high classification accuracy across all lesion types on both internal and external test sets (respectively average area under the curve [AUC]: 0.878 (95% confidence interval [CI]: [0.834–0.918]) and 0.886 (95% CI: [0.813–0.947])) and the confidence score allowed for accurate differentiation between reliable and uncertain predictions. Conclusion Our results demonstrate that the model, associated with confidence measurements, can help in the difficult task of classifying HN squamous lesions by limiting variability and detecting ambiguous cases, taking us one step closer to a wider adoption of AI‐based assistive tools.</p>
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